ABSTRACT The United States is in the midst of an epidemic of prescription drug abuse. In 2016, 3.3 million Americans aged 12 or older reported misusing a prescribed opioid in the past month, with 1.8 million meeting criteria for a prescription opioid use disorder, and over 290,000 being young adults between the ages of 18 and 25. According to the Centers for Disease Control and Prevention, of the 52,404 opioid overdose deaths that occurred in 2015, almost one-quarter involved a prescription opioid, such that the number of people in the U.S. who die each day from overdose of prescription opioids has quadrupled since 1999. This public health crisis was fueled in part by the well-intended efforts of clinicians to better treat chronic pain. Opioid prescriptions almost tripled between 1991 and 2011, and in 2016, clinicians wrote an estimated 215 million prescriptions for these medications, making them highly available in the community reservoir. Yet, despite the growth in opioid prescriptions, the use of opioids for treatment of chronic pain is not an evidence-based intervention. In fact, as evaluation data accumulate, it is becoming clear that outcomes are often poorer for patients on opioid therapy, and that counterintuitive functional improvements are appreciated when the medications are tapered. An oft- cited but untested explanation for this finding is the phenomenon of opioid-induced hyperalgesia (OIH), a theorized state of increased pain sensitivity secondary to ongoing opioid use. Unknown is the degree to which OIH contributes to the chronic pain experience for patients, as is the degree to which opioid taper would improve pain sensitivity. Proposed is an innovative observational pilot study designed to measure the effect of opioid taper on experimental pain perception in patients with chronic pain, thereby providing a proof-of-concept study of OIH, and an empirical foundation for evidence-based treatment in this patient population. Specifically, in a well-characterized sample of chronic pain patients on high-dose opioid therapy (?200mg morphine equivalent dose[MED]/day), we will examine responses to experimental pain stimuli as they undergo a prescribed opioid taper to a target dose of ?90mg MED/day. Using both cold-pressor and quantitative sensory testing pain induction techniques, evoked, spinal and supra-spinal pain responses will be measured at weekly intervals over the course of the active taper, and once stabilized, at monthly intervals up to 12months. In addition to characterizing patterns of pain perception over time, (1) functional outcomes related to opioid taper, and (2) variables related to the patient (age, gender, ethnicity), chronic pain condition (duration, severity), and opioid therapy (dose, potency, duration of use) will be evaluated as predictors of pain response and taper outcomes. Acknowledging the significant health risks associated with opioid therapy for the patient and the community, it is critical that clinicians have evidence of its efficacy and safety. It is anticipated that study findings will explicate the role opioid therapy plays in pain perception in patients with chronic pain, thereby providing evidence-based guidance for opioid pharmacotherapy.